The NM_000156.6:c.148A>C (p.Met50Leu) variant in GAMT has been previously reported in one individual with guanidinoacetate methyltransferase deficiency (PMID: 17101918). This variant is absent from population databases (PM2_Supporting). The affected individual previously reported (PMID: 17101918) was a homozygote for the variant and had a low creatine peak on brain MRS, elevated urinary GAA, low creatine/creatinine ratio, with DNA sequence analysis of GAMT (PM3_Supporting, PP4_Strong). The p.Met50Leu variant is a missense variant that is predicted damaging by in-silico missense predictors (REVEL score 0.923) (PP3). This variant was shown to result in undetectable GAMT enzymatic activity when transfected into GAMT-deficient fibroblasts (PMID: 24415674) (PS3_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic for guanidinoacetate methyltransferase (GAMT) deficiency. GAMT-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiencies Variant Curation Expert Panel (CCDS VCEP) (Specifications version 1.1.0): PS3_Supporting, PM2_Supporting, PM3_Supporting, PP3, PP4_Strong (Classification approved by the ClinGen CCDS VCEP on March 9, 2023)